Shedding of various products from the cell surface of cancer cells may have an important role in loss of adhesion, metastasis, generation of immune-blocking factors and other pathophysiologic aspects of cancer. Human glioma cells in tissue culture produce and shed in the media much greater amounts of glycosaminoglycans (GAGs) than normal glial cells. Glycosaminoglycans are polyanionic compounds, usually bound covalently to a protein core. They are a prominent component of the cell surface and are implicated in cell-cell interaction. There is also evidence for existence of hyaluronidase-sensitive protective coats on some neoplastic cell lines including gliomas, and it has been suggested that the protective GAG coat may impede the immune response and the efficacy of chemotherapy. Our objective was to modify or prevent the synthesis and shedding of GAGs in human glioma cells in culture, and possibly to render them more susceptible to chemotherapy and more immunologically responsive. For this purpose we use singly or in combination, the differentiating agents dimethyl sulfoxide (DMSO), sodium butyrate, retinoic acid, and dexamethasone. These agents are known to affect the synthesis of GAGs in other systems.